Association of PNPLA3 Polymorphisms in Patients with Metabolic Dysfunction Associated Steatotic Liver Disease in North Coastal Andhra Pradesh: A Case-Control Study

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver diseases. It is indeed the leading cause of liver-related morbidity and mortality worldwide. The increasing prevalence of obesity, type 2 diabetes, and metabolic syndrome is leading to a rise in cases of MASLD globally. Genetic predisposition plays a significant role in MASLD development. PNPLA3 rs738409 polymorphism is associated with increased liver fat accumulation and can influence the progression of liver disease. Individuals carrying the variant may have a higher risk of developing conditions like MASLD and other liver complications.

Aim: This study aimed to investigate the relationship between MASLD susceptibility and PNPLA3 polymorphisms in a cohort from North Coastal Andhra Pradesh, India.

Methods:A total of 300 individuals, 150 MASLD cases (93 male, 57 female; mean age: 42.89±11.31 years), and 150 healthy controls (67 male, 83 female, mean age: 40.07±10.43 years) were included in the study. DNA was isolated from peripheral blood using the salting out method. The genotypes of PNPLA3 were determined by the PCR-RFLP (restriction fragment length polymorphism).

Results: The frequencies of rs738409 genotypes CC, CG, and GG were 40%, 36%, and 24% in MASLD cases, while in the control group, they were 23%, 70%, and 7%, respectively. The Chi square test statistic was 38.7871 with ap value of less than 0.0001 indicating a significant difference in genotype distribution between cases and controls. Individuals with the GG genotype have approximately 4.42 times higher odds of having the condition compared to those with the CC genotype.

Conclusion: This study concludes that PNPLA3 (rs738409) polymorphisms may play a key role in MASLD  susceptibility in the cohort. Additionally, the higher prevalence of the CG genotype in controls, where G is the mutant allele, suggests that the CG genotype may confer a protective effect against MASLD. The GG is associated with increased risk. These findings indicate the genetic basis of MASLD and the importance of genotypic variation in disease risk assessment.  particularly CG and GG, were observed to play a crucial role in determining the risk and

susceptibility to MASLD. Correlating disease stage with BMI and biochemical parameters like AST, ALT, along with comprehensive clinical follow-up, could enhance treatment outcomes.